Peptide-containing liposomes, immunogenic liposomes and methods of preparation and use

• US 5,916,588 A
• Filed: 05/25/1995
• Issued: 06/29/1999
• Est. Priority Date: 04/12/1984
• Status: Expired due to Fees

• Current Assignee: Transave Inc. (Insmed Incorporated)
• Original Assignee: The Liposome Co., Inc. (Perrigo Company PLC)
• Inventors: Weiner, Alan L., Alving, Carl R., Janoff, Andrew S., Estis, Leonard, Popescu, Mircea C., Keyes, Lynn D., Recine, Marie S.
• Primary Examiner(s): ACHUTAMURTHY, PONNATHAPURA N
• Application Number:
  US08/452,549
• Time in Patent Office: 1,496 Days
• Field of Search: 424/450, 424/184.1, 424/193.1, 424/195.11, 424/196.11, 424/204.1, 424/206.1
• US Class Current: 424/450
• CPC Class Codes: A61K 2039/55555 Liposomes; Vesicles, e.g. nanoparticles; Spheres, e.g. nanospheres; Polymers
• CPC Class Codes: A61K 39/39 characterised by the immunostimulating additives, e.g. chemical adjuvants
• CPC Class Codes: A61K 9/1271 Non-conventional liposomes, e.g. PEGylated liposomes, liposomes coated with polymers liposome as conjugate A61K47/6911

Abstract

A high integrity liposome comprising at least one stabile lipid and at least one peptide-like therapeutic agent associated with the liposome, adapted for parenteral administration to an animal, including a human, and method according to manufacture and use.

Immunizing dosage forms comprising a liposome and an immunogen, wherein the liposome and immunogen are present in an immunization dose. Additionally, a dosage form, including such form particularly adapted to producing an immune response, comprising a salt according to an organic acid derivative of a sterol and an immunogen are present in an immunization dose, and method according to uses is disclosed. Further, a dosage form, including such form particularly adapted to producing an immune response, comprising dimyristolyphosphatidylcholine (DMPC)/cholesterol liposomes, optionally in an aluminum hydroxide gel, and an immunogen wherein the DMPC/cholesterol and immunogen are present in an immunization dose, and method according to use.

Claims

1. An immunizing dosage form which comprises an adjuvant liposome comprising:

(i) a lipid which consists essentially of an organic acid derivative of a sterol; and

,

(ii) an antigenic peptide,

wherein the organic acid derivative of the sterol comprises an organic acid attached to the sterol at a hydroxyl of the sterol by an ether or ester linkage, wherein the organic acid is selected from the group consisting of carboxylic, dicarboxylic, polycarboxylic, hydroxy, amino and polyamino acids and wherein the liposome is present in the dosage form in an immunization dose.

2. The dosage form of claim 1, wherein the sterol is cholesterol.

3. The dosage form of claim 1, wherein the acid is a dicarboxylic acid having up to seven carbon atoms.

4. The dosage form of claim 3, wherein the acid is succinic acid.

5. The dosage form of claim 1, wherein the acid is the hydroxy acid citric acid.

6. The dosage form of claim 1, wherein the sterol comprises a salt form of the organic acid.

7. The dosage form of claim 6 wherein the salt form is a tris(hydroxymethyl)aminomethane salt.

8. The dosage form of claim 1, wherein the liposome is a multilamellar liposome.

9. The dosage form of claim 1, wherein the liposome has a size of about 1 micron.

10. The dosage form of claim 1, wherein the antigenic peptide is a viral peptide.

11. The dosage form of claim 1, further comprising an immunomodulator.

12. The dosage form of claim 11, wherein the immunomodulator is a cytokine.

13. The dosage form of claim 1, comprising a pharmaceutically acceptable carrier.

14. The dosage form of claim 1, wherein the sterol is cholesterol hemisuccinate.

15. The dosage form of claim 14, wherein the salt form is the tris salt of cholesterol hemisuccinate.

16. The dosage form of claim 14, wherein the immunogen is a viral peptide.